LAUSR

Neutrophils are the most abundant circulating leukocytes in humans and are amongst the first responders to be recruited to sites of injury and infection in response to inflammatory cues. These short-lived cells are formed by granulopoiesis in the bone marrow. Mature neutrophils are released into the circulation in a chemokine-regulated, circadian fashion (1). In the absence of stimulatory signals, neutrophils will circulate for ~1 day before becoming senescent and homing back to the bone marrow. In the presence of stimulating signals, neutrophils migrate to inflammatory sites along gradients of chemokines. Exit from blood vessels is usually selectinand integrin-dependent, although certain sites with highly specialised vasculature (e.g., lung, liver, brain) are characterised by extravasation that is supported by alternative adhesion molecules (2). In contrast, interstitial neutrophil migration occurs in an integrin-independent fashion. Upon reaching inflammatory sites, neutrophils clear cell debris and act as the first line of cellular immunity against invading pathogens. Once their job is done, neutrophils either undergo apoptosis, releasing “eat-me” signals and are cleared by professional phagocytes; or can migrate away from inflamed tissues, promoting tissue healing responses. If these processes are dysregulated, neutrophils can release their toxic components into surrounding tissues, leading to bystander cell damage and chronic inflammation. This Research Topic on neutrophil biology aims to highlight some of the latest developments in the diverse roles of neutrophils in host immunity, inflammation and tissue repair. Neutrophils become involved in inflammatory processes through rapid, directed migration towards sites of tissue damage. Bader et al. examined the b2 integrin-dependency of neutrophil recruitment to transected tailfins in zebrafish larvae via generation of a CRISPR/Cas9 genetic deletion of CD18, identifying a reduction in neutrophil trafficking to the sterile inflammation site, alongside an increase in neutrophil number found in the circulation. Two reports evaluated the contribution of individual signaling intermediates in diverse neutrophil functions, with a particular focus on neutrophil trafficking. Yan et al. explored the function of the Gai2 – regulator of G (RGS) protein interactions, showing that they are required for fine-tuning neutrophil trafficking as well as clearance of aged neutrophils, ultimately avoiding excessive neutrophilic inflammation. Meanwhile, Michael et al. reported that the phosphoinositide 5-phosphatase SHIP2 promotes neutrophil trafficking to sites of inflammation and chemotactic directionality. Directed neutrophil migration